Collagen Type IV as Independent Prognostic Factor for Non-Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4708-4708
Author(s):  
Liljana Hadzi-Pecova ◽  
Gordana Petrusevska ◽  
Irina Panovska ◽  
Svetlana Stankovic ◽  
Aleksandar Stojanovik
Keyword(s):  
Basement Membrane ◽  
Hodgkin’S Lymphoma ◽  
Collagen Type ◽  
International Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Collagen Type Iv ◽  
Female Ratio ◽  
Type Iv ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Many attempts have been made recently to improve the prognostic systems for non-Hodgkin’s lymphoma (NHL). There are no available data in the literature regarding the influence of intactness of the basement membrane of the blood vessels on the prognosis of NHL, when compared with the clinical characteristics of the disease. On the other hand, it is known that the integrity of the basement membrane is marker for the aggressiveness of the malignant disorders. In order to analyze the association of the expression patterns of collagen type IV on the prognosis of the patients with NHL we have conducted a retrospective study. We have evaluated 136 patients diagnosed and treated as NHL in the last ten years at the Clinic of Hematology, Medical Faculty -Skopje. All 136 patients with representative tumor tissues were diagnosed with NHL according to the REAL classification (71 patients were diagnosed as diffuse large cell lymphoma, 28 as follicular lymphoma, 24 as small lymphocytic lymphoma and 14 as marginal zone lymphoma). Median age of the patients was 49 years, with male: female ratio 1.5:1.0. The application of international prognostic index (IPI) identified four risk groups with predicted five-years survival rates of 87%, 82%, 18% and 0%, with statistical significance (p< 0.001). Using immunoperoxidase staining we have analyzed the collagen type IV expressing patterns in our group of patients, and defined three tumor invasive grades: high tumor invasive grade as total lack of immunoreactivity for collagen type IV (68 patients), medium-presented as discontinuous expression (56 patients) and low-as a continuous linear expression (14 patients). The 5 year overall survival rate was significantly lower (p<0.01) in patients with high invasive grade than in patients with medium or low invasive grade (54% vs. 78% and 100%). Further, in multivariate analysis collagen type IV expression appeared as an independent survival-predicting factor together with the parameters of the IPI. Our results indicated that the expression of a collagen type IV immunoreactivity could predict the outcome of patients with NHL. However, further studies are needed to define the role of collagen type IV in the future prognostic systems for NHL.

scholarly journals International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for all malignancy grades

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1460-1463 ◽  
Author(s):  
J Hermans ◽  
AD Krol ◽  
K van Groningen ◽  
PM Kluin ◽  
JC Kluin-Nelemans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hodgkin’S Lymphoma ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Population Based ◽  
Hodgkin's Lymphoma ◽  
Intermediate Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).

Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation, response to treatment, and survival--a Groupe d'Etude des Lymphomes de l'Adulte study on 453 patients older than 69 years.

1997 ◽  
Vol 15 (8) ◽  
pp. 2945-2953 ◽  
Author(s):  
Y Bastion ◽  
J Y Blay ◽  
M Divine ◽  
P Brice ◽  
D Bordessoule ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Aggressive Lymphoma ◽  
Prognostic Parameters ◽  
Aggressive Disease ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE To clarify disease characteristics and optimal treatment for elderly patients with non-Hodgkin's lymphoma (NHL), we performed a randomized trial in 453 patients older than 69 years with aggressive lymphoma. PATIENTS AND METHODS Two hundred twenty patients received cyclophosphamide 750 mg/m2, teniposide (VM-26) 75 mg/m2, and prednisone 40 mg/m2/d for 5 days (CVP) and 233 patients received CVP plus pirarubicin (THP-doxorubicin) 50 mg/m2 (CTVP), each for six courses every 3 weeks. RESULTS The median age was 75 years. Most patients had clinically aggressive disease; 30% had one and 53% two or three adverse prognostic parameters as defined by the International Prognostic Index. More patients on the CTVP arm had an elevated lactic dehydrogenase (LDH) level, but the two groups were otherwise well balanced. CTVP treatment was more frequently associated with leukopenia, thrombocytopenia, and infectious complications. Death during chemotherapy occurred in 16% and 21% of patients on the CVP and CTVP arms, respectively (not significant). Forty percent of patients achieved a complete response (CR): 47% on CTVP and 32% on CVP (chi2 = 20.98, P = .0001). The median time to treatment failure (TTF) was 7 months for CTVP versus 5 months for CVP (log-rank test, P < .05). The median survival time was 13 months in both groups; however, the 5-year survival rate was 26% with CTVP versus 19% with CVP (chi2 = 4.68, P < .05). Lymphoma progression was the primary cause of death. CONCLUSION Elderly patients with aggressive lymphoma have an aggressive disease with adverse prognostic parameters at the time of diagnosis. Slightly longer survival was observed for patients treated with an anthracycline-containing regimen.

Pyothorax-Associated Lymphoma: A Review of 106 Cases

2002 ◽  
Vol 20 (20) ◽  
pp. 4255-4260 ◽  
Author(s):  
Shin-ichi Nakatsuka ◽  
Masayuki Yao ◽  
Yoshihiko Hoshida ◽  
Satoru Yamamoto ◽  
Keiji Iuchi ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Pleural Cavity ◽  
Hodgkin's Lymphoma ◽  
Cell Phenotype ◽  
Female Ratio ◽  
Non Hodgkin’S Lymphoma ◽  
Chronic Inflammatory Condition ◽  
Non Hodgkin's Lymphoma ◽  
History Of

PURPOSE: Pyothorax-associated lymphoma (PAL) is a non-Hodgkin’s lymphoma developing in the pleural cavity after a long-standing history of pyothorax. Full details of PAL are provided here.PATIENTS AND METHODS: Clinical and pathologic findings were reviewed in 106 patients with PAL collected through a nationwide survey in Japan.RESULTS: Age of the patients with PAL was 46 to 82 years (median, 64 years), with a male/female ratio of 12.3:1. All patients had a 20- to 64-year (median, 37-year) history of pyothorax resulting from artificial pneumothorax for treatment of pulmonary tuberculosis (80%) or tuberculous pleuritis (17%). The most common symptoms on admission were chest and/or back pain (57%) and fever (43%). Laboratory data showed that the serum neuron-specific enolase level was occasionally elevated (3.55 to 168.7 ng/mL; median, 18.65 ng/mL), suggesting a possible diagnosis of small-cell lung cancer. Histologically, PAL usually showed a diffuse proliferation of large cells of B-cell type (88%). In situ hybridization study showed that PAL in 70% of the patients was Epstein-Barr virus (EBV)-positive. PAL was responsive to chemotherapy, but the overall prognosis was poor, with a 5-year survival of 21.6%.CONCLUSION: This study established the distinct nature of PAL as a disease entity. PAL is a non-Hodgkin’s lymphoma of exclusively B-cell phenotype in the pleural cavity of patients with long-standing history of pyothorax, and is strongly associated with EBV infection. Development of PAL is closely related to antecedent chronic inflammatory condition; therefore, PAL should be defined as malignant lymphoma developing in chronic inflammation.

scholarly journals Prognostic Significance of Bcl-2 Protein Expression and Bcl-2 Gene Rearrangement in Diffuse Aggressive Non-Hodgkin's Lymphoma

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 244-251 ◽  
Author(s):  
Randy D. Gascoyne ◽  
Sheryle A. Adomat ◽  
Stanislaw Krajewski ◽  
Maryla Krajewska ◽  
Douglas E. Horsman ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hodgkin’S Lymphoma ◽  
Gene Rearrangement ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact

Abstract The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P &lt; .01), DFS (32% v 66%, P &lt; .001), and RFS (25% v 59%, P &lt; .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P &lt; .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.

scholarly journals Elevated Serum CD44 Level Is Associated With Unfavorable Outcome in Non-Hodgkin's Lymphoma

Blood ◽  
1997 ◽  
Vol 90 (10) ◽  
pp. 4039-4045 ◽  
Author(s):  
Raija Ristamäki ◽  
Heikki Joensuu ◽  
Kimmo Lappalainen ◽  
Lasse Teerenhovi ◽  
Sirpa Jalkanen
Keyword(s):  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
Unfavorable Outcome ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Cell Surface Glycoprotein ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract CD44 molecule is a cell surface glycoprotein involved in many cell-cell and cell-matrix interactions. Circulating serum CD44 (s-CD44) levels have been found to change in parallel with response to therapy, but little is known about the predictive or prognostic significance of s-CD44. In the present study, we measured s-CD44 levels in sera taken before treatment from 194 patients with non-Hodgkin's lymphoma using a chemiluminescence-enzyme immunoassay method. All except 1 patient were regularly followed-up after therapy at least for 60 months (range, 33 to 143 months). The median pretreatment s-CD44 level was 440 ng/mL (range, 13 to 1,220 ng/mL). Only 32% of the 92 patients with an International Prognostic Index (IPI) score of 0 or 1 had an s-CD44 concentration higher than the median as compared with 67% of the patients with an IPI score ≥2 (P < .0001). Patients with lower than the median s-CD44 achieved more often a complete remission to therapy (P = .0002) and had better survival (P = .007) than those with higher s-CD44 levels. However, in a multivariate analysis, only the IPI score had independent prognostic value (P < .001). The findings were similar if only the patients with diffuse large-cell lymphoma (n = 51) were included in the analysis, but among patients with low-grade lymphoma, the median s-CD44 level was not significantly associated with the IPI or survival. In conclusion, a high s-CD44 level at diagnosis is associated with a high IPI score, poor response to treatment, and unfavorable outcome in non-Hodgkin's lymphoma.

Liposome-Encapsulated Doxorubicin in Combination With Standard Agents (cyclophosphamide, vincristine, prednisone) in Patients With Newly Diagnosed AIDS-Related Non-Hodgkin's Lymphoma: Results of Therapy and Correlates of Response

2004 ◽  
Vol 22 (13) ◽  
pp. 2662-2670 ◽  
Author(s):  
Alexandra M. Levine ◽  
Anil Tulpule ◽  
Byron Espina ◽  
Andy Sherrod ◽  
William D. Boswell ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Liposomal Doxorubicin ◽  
International Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Newly Diagnosed ◽  
Viral Control ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact ◽  
Mdr 1

Purpose To evaluate the safety and efficacy of liposomal doxorubicin (Myocet; Medeus Pharma Ltd, Herts,UK) when substituted for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Secondary objectives were to assess the impact of HIV viral control on response and survival, and to correlate MDR-1 expression with outcome. Patients and Methods Liposomal doxorubicin at doses of 40, 50, 60, and 80 mg/m2 was given with fixed doses of cyclophosphamide, vincristine, and prednisone every 21 days. All patients received concurrent highly active antiretroviral therapy. NHL tissues were evaluated for multidrug resistance (MDR-1) expression. Results Twenty-four patients were accrued. 67% had high or high-intermediate International Prognostic Index scores; the median CD4 lymphocyte count was 112/mm3 (range, 19/mm3 to 791/mm3). No dose-limiting toxicities were observed at any level, with myelosuppression being the most frequent toxicity. Overall response rate was 88%, with 75% complete responses (CRs), and 13% partial responses. The median duration of CR was 15.6+ months (range, 1.7 to 43.5+ months). Effective HIV viral control during chemotherapy was associated with significantly improved survival (P = .027), but CRs were attained independent of HIV viral control. MDR-1 expression did not correlate with response, suggesting that the liposomal doxorubicin may evade this resistance mechanism. Conclusion Liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is active in AIDS-NHL, with complete remissions achieved in 75% independent of HIV viral control or tissue MDR-1 expression. HIV viral control is associated with a significant improvement in survival. Additional studies are warranted.

Development and Measurement of Guideline-Based Indicators for Patients With Non-Hodgkin's Lymphoma

2011 ◽  
Vol 29 (11) ◽  
pp. 1436-1444 ◽  
Author(s):  
Lianne Wennekes ◽  
Petronella B. Ottevanger ◽  
John M. Raemaekers ◽  
Harry C. Schouten ◽  
Marjorie W.E. de Kok ◽  
...  
Keyword(s):  
The Netherlands ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Aggressive Lymphoma ◽  
Diagnostic Process ◽  
Non Hodgkin’S Lymphoma ◽  
Improvement Potential ◽  
Non Hodgkin's Lymphoma

Purpose Patients with cancer are not always treated according to available guidelines. Factors such as age and comorbidities are frequently used as arguments for nonadherence. The aim of this study was to measure guideline adherence with guideline-based indicators for patients with non-Hodgkin's lymphoma (NHL) and to examine the need for improvement, considering relevant arguments. Methods A RAND-modified Delphi procedure was used to systematically develop NHL indicators. We evaluated their improvement potential (defined as < 90% score) in a random sample of patients with NHL (N = 431) diagnosed in 2006-2007 in 22 hospitals in the Netherlands with data from medical records. Multilevel logistic regression analyses were used to estimate the relationship between indicator scores and factors: comorbidity index (combined with age), stage, patient's objections, and lymphoma type. Scores were adjusted for significant factors. Results Of the 20 indicators developed, 16 had improvement potential. Scores were lowest for assessment of International Prognostic Index, 21%; imaging of neck, thorax, and abdomen and bone marrow examination during the diagnostic process, 23%, and after chemotherapy, 37%; adequate pathology reporting, 11%; and multidisciplinary discussion of patients, 21%. Scores for eight indicators were better for patients with a low Charlson index, stage III or IV disease, no objections to care, and aggressive lymphoma. After adjustments, adherence to all but one indicator (administration of the combination of rituximab and cyclophosphamide-doxorubicin-vincristine-prednisone) remained < 90%. Conclusion In the Netherlands, almost all indicators for NHL needed improvement. This should be evaluated in other countries as well. International efforts should be undertaken to improve the quality of care of this often curable malignancy.

Multicenter Phase II Trial of Immunotherapy With the Humanized Anti-CD22 Antibody, Epratuzumab, in Combination With Rituximab, in Refractory or Recurrent Non-Hodgkin's Lymphoma

2006 ◽  
Vol 24 (24) ◽  
pp. 3880-3886 ◽  
Author(s):  
Sandra J. Strauss ◽  
Frank Morschhauser ◽  
Juergen Rech ◽  
Roland Repp ◽  
Philippe Solal-Celigny ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Objective Response ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose A multicenter, single-arm study examining efficacy and toxicity of epratuzumab combined with rituximab was conducted in patients with recurrent or refractory non-Hodgkin's lymphoma. Patients and Methods Sixty-five patients were enrolled; 34 patients with follicular lymphoma (FL), 15 patients with diffuse large B-cell lymphoma (DLBCL), and 16 patients with other lymphomas. The patients had received a median of two prior therapies (range, 1 to 4); 23% had received rituximab. Epratuzumab was given at 360 mg/m2 intravenously over 60 minutes followed by infusion of 375 mg/m2 rituximab, weekly for 4 consecutive weeks. Results Combination therapy was well tolerated without greater toxicity than rituximab alone. The objective response (OR) rate was 47% (30 of 64) in assessable patients (46%; 30 of 65 in all patients), being highest in FL (64%; 21 of 33) and DLBCL (47%; seven of 15), and with 24% (eight of 33) and 33% (five of 15) achieving complete response (CR) or complete response unconfirmed (CRu) in these two groups, respectively. Two of six patients with marginal zone lymphoma responded to treatment (one CR). There was a trend for the response rates to be higher in patients with low prognostic index scores (statistically significant with respect to the Follicular Lymphoma International Prognostic Index score in FL patients), with 12 FL patients and three DLBCL patients in groups 0 to 1 having OR (CR/CRu) rates of 83% (33%) and 100% (100%), respectively. The median duration of response was 16 months for FL, with five patients currently progression free for 18 months to 30 months, and 6 months for DLBCL, with two patients currently progression free for 12 months and 18 months. Conclusion Epratuzumab combined with rituximab was well tolerated, demonstrating promising antilymphoma activity that warrants additional study.

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